1. Technical Field of the Invention
The present invention relates to a novel mammalian CUDR cDNA which encodes a cancer marker and use of CUDR gene in the diagnosis of cancer progression and therapeutic response.
2. Technical Background of the Invention
Cancer diseases account for nearly one-quarter of deaths in the United States, exceeded only by heart diseases. The disease contributes to a major financial burden to the community and to individual. In general, cancer patients often undergo chemotherapy and radiotherapy. However, the treatment outcome is not always satisfactory. There are many reasons that patients are refractory to treatment, e.g. advanced stage of cancer, development of drug resistance.
The importance of the development of a marker for early detection of cancer and the effectiveness of cancer therapeutic response is suggested. There have been many molecular tumor markers used in clinical situations. Many of these markers were found to be associated with only a small proportion of tumors, preventing their widespread use in diagnosis. Furthermore, altered expression of some of these genes has also been reported in normal cells, which leads to false-positive results. For example, prostate-specific antigen (PSA) is now used for yearly evaluations of prostate cancer in most male patients in the United States. However, about one-third of the patients with an elevated PSA were later on to show not to have a malignant form of prostate cancer. In other cases, serum carcinoembryonic antigen (CEA) levels are now used to monitor disease progression and response to therapy in patients with colorectal cancer. However, only a proportion of colorectal cancers demonstrated elevated CEA levels at the time of diagnosis. More reliable serum markers are therefore needed to improve colorectal cancer diagnosis and to follow cancer progression. For most other types of cancer, reliable molecular markers are currently not available.
In order to fully understand the pathogenesis of cancer, it will be necessary to identify novel genes that may be involved in cancer development and drug resistance. A novel CUDR gene (a 2.2 kb transcript), identified by RT-PCR based differential display, was found to be over-expressed in doxorubicin resistant tumor sublines such as human squamous carcinoma A431 and hepatocellular carcinoma HepG2 cells. Furthermore, the gene is barely detectable in human normal tissues except placenta. By comparing the expression between normal-tumor matched tissues by RT-PCR, the gene was found to overexpress predominantly in colon cancer, lung cancer, cervical cancer and estrogen receptor alpha negative breast cancer tissues. The overexpression of CUDR in tumor tissue of patients and in cells developed drug resistance indicated that the gene may act as a marker for cancer progression and also therapeutics response.